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Mechanisms of Chronic Alcohol Exposure-Induced Aggressiveness in Cellular Model of HCC and Recovery after Alcohol Withdrawal.

Abstract : Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments. Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to chronic alcohol exposure (CAE), at different doses for 6~months followed by 1-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270~mM dose, CAE decreased cell viability by about 50% and 80%, respectively, in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of cancer stem cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3β signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly, we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies. Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03703795
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Soumis le : vendredi 24 juin 2022 - 12:02:17
Dernière modification le : vendredi 5 août 2022 - 11:26:18

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Constance Marié, Grégory Fouquet, Anoïsia Courtois, Rabbind Singh Amrathlal, Nicolas Jankovsky, et al.. Mechanisms of Chronic Alcohol Exposure-Induced Aggressiveness in Cellular Model of HCC and Recovery after Alcohol Withdrawal.. Cellular and molecular life sciences : CMLS, 2022, 79 (7), pp.366. ⟨10.1007/s00018-022-04387-y⟩. ⟨hal-03703795⟩

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